Saturday, March 31, 2012

Cinematic enfant terrible Gaspar Noé has been shocking audiences with his artistic films of graphic violence for over 20 years. In IMDb he is quoted as saying:

"There is no line between art and pornography. You can make art of anything. You can make an experimental movie with that candle or with this tape recorder. You can make a piece of art with a cat drinking milk. You can make a piece of art with people having sex. There is no line. Anything that is shot or reproduced in an unusual way is considered artistic or experimental."

I haven't seen a Noé film myself, so I can't offer any personal opinions. The descriptions themselves are so graphic and repellent that I've avoided them.

What can Noé and neuroscience possibly have in common? Neurologist/cognitive neuroscientist Dr. Guillén Fernández and colleagues have been showing clips from Irréversible to participants in fMRI studies.

The film employs a non-linear narrative and follows two men as they try to avenge a brutally raped girlfriend. ... Several reviewers declared it one of the most disturbing and controversial films of 2002.1

Why would researchers show this film to [perhaps unsuspecting]2 college students? To quickly induce a state of extreme psychological stress. In brief, Fernandez et al. are interested in studying the brain under acute stress. A PubMed search suggests there are at least 16 articles using this methodology.

During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes.

The data analysis strategy employed the methods of "neurocinematics" (Hasson et al., 2008) to find inter-subject correlations (ISCs) in the BOLD response during free viewing of the film clips. Then the regions that responded to the aversive film to a greater extent were identified. These included areas associated with interoception and autonomic-neuroendocrine control, peripheral stress effector systems and catecholaminergic signaling, and sensory and attentional (re)orienting.

Then "multisession tensorial probabilistic independent component analysis" was used to test for functional connectivity between these regions, which overlapped with the "salience network" observed in resting state studies (Seely et al., 2007). Finally, pharmacological manipulations suggested that the stress-induced connectivity within this network was decreased by blocking β-adrenergic receptors [via propranolol], but not cortisol synthesis [via metyrapone].

1 Watch the trailer for Irreversible [NOTE: This video has been age-restricted].

2 Participants with "regular exposure to extremely violent movies or computer games" are excluded from the studies.

3 The presented film clips were described as follows:

Fragments (both 140 s) from two different movies entitled "Irréversible" (2002), by Gaspar Noé, and "Comment j’ai tué mon père" (2001), by Anne Fontaine, were selected to serve as aversive and neutral control movie clips, respectively. ... Matching for audiovisual characteristics (see table S1) was performed by the authors by selecting aversive and neutral clips out of a set of candidate clips which best matched on the following measures: presence of faces in the foreground, presence of background actors, amount of distinct camera movements, and percentage of time the camera was moving. Selected aversive scenes contained extreme male-to-male aggressive behavior and violence in front of a crowd. Neutral control scenes also contained people interacting in the foreground in the presence of a background crowd. Fragments were equalized in luminance. Both movies are French spoken, but selected movie clips contained minimal speech.

Estimating the analytic flexibility of functional neuroimaging: Implications for uncertainty and bias in cognitive neuroscience

Joshua Carp; University of Michigan

How vulnerable is the field of cognitive neuroscience to bias? According to a recent mathematical model, the potential for scientific bias increases with the flexibility of analytic modes. In other words, the greater the range of acceptable analysis strategies, the greater the likelihood that published research findings are false. Thus, the present study sought to empirically estimate the analytic flexibility of fMRI research. We identified five pre-processing decisions and five modeling decisions for which two or more analysis strategies are commonly used in the research literature. By crossing each of these strategies and decisions, we identified 4,608 unique analysis pipelines. Next, we applied each of these pipelines to a previously published fMRI study of novelty detection in an auditory oddball task. We found that activation estimates were highly dependent on methodological decisions: contrasts that yielded significant positive activation under one pipeline were associated with non-significant positive activation or even with negative activation under other pipelines. Some analysis decisions contributed more to this variability more than others, and each decision exerted a unique pattern of variability across the brain. The effects of a given decision also varied across contrasts, subjects, and other analysis parameters. In sum, we found considerable quantitative and qualitative variability across analysis pipelines, suggesting that the results of cognitive neuroimaging experiments may be more uncertain than they seem. Indeed, given a supercomputer, a sufficiently motivated analyst might observe almost any imaginable pattern of results.

Food is a highly motivating stimulus in our environment. We eat for many non-homeostatic reasons, such as celebration, comfort, and hedonic pleasure. Novel investigations of the neural basis of healthy and disordered eating reveal that throughout the multisensory process of food consumption, sensory, reward processing and cognitive control brain regions work together to keep track of how rewarding the experience is and help us decide whether or not to continue eating. A complete cognitive neuroscience model of food motivation requires understanding the sensory, reward, and cognitive mechanisms associated with healthy eating, and how those mechanisms can run amok. The first talk will review recent fMRI studies in lean individuals which identify how neural systems involved in retrieving food taste and reward information contribute to food motivation and food-related decision making. The second talk describes a study that uses multi-modal (visual and auditory) food cues to examine a dynamic, distributed reward-related network specifically associated with subjective ratings of cue-induced desire to eat in lean and obese women. The third talk provides evidence suggesting that overweight individuals show deficits in dopamine-dependent learning, as indicated by reduced error signal generation in the OFC and ventral striatum, and impaired insula-mediated flavor-nutrient conditioning. The final talk will bring together evidence across the spectrum from healthy to disordered eating behaviors by examining the neural circuitry underlying differences in food motivation between anorexia, healthy weight, obese, and Prader-Willi syndrome populations. Together, the talks will provide a stimulating introduction to the networks involved in food motivation.

Context Sexual sadism is a psychiatric disorder in which sexual pleasure is derived from inflicting pain, suffering, or humiliation on others. While the psychological and forensic aspects of sexual sadism have been well characterized, little is known about the neurocognitive circuitry associated with the disorder. Sexual sadists show increased peripheral sexual arousal when observing other individuals in pain. The neural mechanisms underlying this unusual response are not well understood. We predicted that sadists relative to nonsadists would show increased responses in brain regions associated with sexual arousal (amygdala, hypothalamus, and ventral striatum) and affective pain processing (anterior cingulate and anterior insula) during pain observation.

The subtitle of the paper is Preliminary Findings and one must keep this in mind, given the small n in the groups.

The experimental design involved presenting a set of three images depicting (a) one person inflicting pain upon another ("Pain"), and (b) control images with two people but no pain inflicted ("No Pain"). The participants rated the severity of pain inflicted for each stimulus set on a 0-4 scale. A third condition depicted one person causing damage to an object, but those results were not presented in the paper.

A. Over a period of at least 6 months, recurrent, intense sexually arousing fantasies, sexual urges, or behaviors involving acts (real, not simulated) in which the psychological or physical suffering (including humiliation) of the victim is sexually exciting to the person.

B. The person has acted on these sexual urges with a nonconsenting person, or the sexual urges or fantasies cause marked distress or interpersonal difficulty.2

So it comes as no surprise that brain regions associated with sexual arousal were predicted to show greater activity to Pain in the sadists. What are the "sexual arousal areas"? According to the authors, these include the amygdala, hypothalamus, and ventral striatum. The problem is that none of these areas is selectively involved in sexual arousal [with the possible exception of specific hypothalamic nuclei]. In fact, the amygdala is more often related to fear, so greater activity might also be expected in those who take the perspective of the victim.

The other major prediction was that activity in the "affective pain areas" (anterior cingulate cortex and anterior insula)3 would be greater to Pain images in the sadists, because they are actually more sensitive to the suffering of others. This might seem counterintuitive in such callous individuals, but...

In any scenario where pain is imminent, sadists may pay closer attention than nonsadists to the thoughts and feelings of the victim because this enhances their sexual arousal when pain is inflicted. In other words, whereas sadists lack sympathy for their victims, they may exhibit empathy (simulating their victims' feelings) when consistent with their goals.

In support of this view, the sadists rated Pain pictures as higher in severity than the nonsadists did. The two groups did not differ in their ratings of No-Pain pictures. In the future, comparison to a control population of nonviolent offenders would be helpful.

Since Sand Ridge does not have its own scanning facility [gasp!], running the fMRI experiment involved use of a mobile unit.

Kent Kiehl outside the mobile scanner he has used to look at the brains of inmates at a New Mexico prison. Credit: Nature News.

What were the results of the imaging study? The sadists showed greater activity to Pain (vs. No-Pain) in the left amygdala, but the nonsadists did not. The right ventral striatum showed a main effect of group (greater activation in the sadists) which did not differentiate between Pain and No-Pain pictures. No significant effects were observed in the hypothalamus.

Overall, it's not clear whether the amygdala result is related to sexual arousal at all. The participants were not asked if they found the pictures arousing (nor were any peripheral signs of this measured).

Finally, activity in a region of the left anterior insula showed a positive correlation with pain severity ratings in the sadists but not in the nonsadists. This could mean they were more attuned to the suffering of others, but it could also mean they experienced a higher level of disgust (unlikely, but see Jabbi et al., 2008).

The authors end on a speculative (and controversial) note, wondering whether the "neural abnormalities" of incarcerated sadistic sexual predators would generalize to those who engage in consensual sadism:

It is interesting to consider whether the neural abnormalities that characterize incarcerated sexual sadists generalize to individuals in the community with sadistic sexual preferences. Sadists who offend may differ from those who do not in early environment (eg, abuse or inadequate social and family environment). Individuals involved in consenting sadomasochistic relationships are also different from criminal sadists because criminal sadists do not generally engage in sadomasochism, nor do those in sadomasochistic relationships generally victimize others. Nonetheless, all experience sexual arousal to pain infliction. Therefore, whether the present results generalize to all sadists is a question for future research.

Footnotes

1 This scale is:

an 11-item scale rated according to history of sexual behavior. Items are rated yes (1 point) or no (0 points) and include the following: (1) engages in gratuitous violence toward or wounding of victim; (2) exercises power, control, or domination over victim; (3) humiliates or degrades victim; (4) is sexually aroused by the act; (5) tortures victim or engages in acts of cruelty to victim; (6) shows evidence of ritualism in offense; (7) abducts or confines victim; (8) inserts object or objects into victim's bodily orifice or orifices; (9) mutilates sexual parts of victim's body; (10) mutilates nonsexual parts of victim's body; and (11) keeps trophies (eg, underwear or identification) of victim or keeps records of the offense. To meet sexual sadist criteria, an offender's behavior must include at least 4 items (3 of which must be items 2-5 or item 9).

The change in the B. criterion from DSM-IV to DSM-IV-TR represents one of the few changes in criteria from DSM-IV to DSM-IV-TR. This change was made to all of the paraphilias which involved a victim, to remove any ambiguity about whether acting out sexual urges with others was sufficient for a diagnosis; some had argued that an individual with a paraphilia who was not distressed about his or her behavior could not be diagnosed with a paraphilia, and this new wording allowed for a diagnosis to be made in such a circumstance.

The addition of "nonconsensual" was also instituted in 2000, thereby depathologizing those who engage in consensual BDSM activities.

3 To avoid becoming too pedantic, I won't expound on how anterior cingulate and insular cortices are not specific to affective pain processing. These two regions are activated by most everything:

We propose that the ventral stream of projections from the striate cortex to the inferotemporal cortex plays the major role in the perceptual identification of objects, while the dorsal stream projecting from the striate cortex to the posterior parietal region mediates the required sensorimotor transformations for visually guided actions directed at such objects.

Other researchers have extended the degree of specialization shown by the visual and semantic systems. Some studies have suggested there might be category-specific processing of living and non-living things (e.g., animals and tools), although the reasons for this specialization are a matter of debate (Caramazza & Shelton, 1998; Thompson-Schill et al., 1999). Chao and Martin (2000) found that pictures of tools activated the left posterior parietal cortex in the dorsal stream to a greater extent than pictures of animals, houses, and faces. The idea is that objects with salient motor-based properties (hammers) should recruit "vision for action" cortical regions to a greater extent than objects without such affordances (zucchini).

More recently, Almeida and colleagues (2008) used two different visual masking techniques in a priming study designed to isolate the influence of the dorsal stream:

Their results suggested that categorically related primes suppressed under CFS still facilitated reaction times to tool targets, but not to animal targets. In other words, participants were faster to classify tools when preceded by a picture of a tool than when preceded by a picture of an animal, and this priming effect held up when the ventral stream was unavailable.

A new study by Sakuraba et al. (2012) wanted to clarify which specific attributes of tools are processed by the dorsal stream, so they used a greater variety of categorically related and unrelated prime stimuli suppressed under CFS, as shown below.

Fig. 1 (Sakuraba et al., 2012). Procedure using CFS. Different images were presented into the subject's left and right eyes by using anaglyphs. Dynamic high-contrast random-noise patterns (10 Hz) were presented to the dominant eye, while low-luminance, low-contrast prime stimuli were presented to the nondominant eye. Subjects could report the dynamic noise but not the static image. Each trial started with a fixation cross for 500 ms, followed for 200 ms by a prime stimulus suppressed by CFS. Finally, a target stimulus masked by 70% additive noise was presented until the subject responded (maximum duration: 3 s) by pressing a key to indicate the category of the target stimulus.

One of the manipulated attributes was shape. Non-elongated ("stubby") tools, elongated vegetables, and stubby vegetables1 were used as primes for elongated tools (e.g., hammer, ax, fork, etc.). Other conditions used geometric shapes as primes.

In Experiment 2, we used tool pictures without elongated shape components, namely stubby tools (e.g., a punch, a squeezer, a mouse, and so on). ... In Experiment 3, elongated stick figures were used as prime stimuli. In Experiment 4, elongated and stubby vegetable pictures were presented as prime stimuli. Because the elongated shapes involve an orientation component, we could not exclude the possibility that orientation, rather than shape attribute, explained the results. Therefore, we conducted Experiment 5 to clarify this. We used elongated stick figures, diamond shapes, and cut circles that were rotated in 45° increments as prime stimuli.

Interestingly, membership in the category of tools per se was irrelevant; it was the shape of the prime that mattered.

This throws a wrench (so to speak) into the dorsal stream as the vision for action pathway, unless you normally use a zucchini to pound your nails into the wall. The less dramatic interpretation is that the categorical information obtained by viewing pictures of tools isn't neatly respected by the dorsal stream, but visually-guided reaching and grasping remain unscathed.

Footnote

1 The "stubby vegetables" were my favorite part of the paper.

2 You might want to quibble with the size and functional significance of the priming effect. Although statistically significant, it was rather small.

Saturday, March 17, 2012

Marina Malvada is a painter, musician and chocolatier who makes anatomically correct skulls out of the finest imported chocolate. How does she get them to look so realistic? The confections are cast from an actual human skull:

I once had the unique opourtunity to borrow an authentic human skull and make a mold of it to cast in plaster. When I purchased my supplies, I discovered the availability of food grade materials, and instantly, the notion of chocolate skulls came to mind!

These chocolate skulls are available in three flavors: bone chocolate (a "signature blend of Belgian white and creamy milk chocolate"), dark chocolate, and semi-sweet chocolate.

Friday, March 09, 2012

Since sub-optimally designed and analyzed fMRI studies continue to influence the field, there should be some mechanism for identifying discredited publications. This discussion was initiated by Professor Dorothy Bishop's critical analysis of a flawed paper. In response, Dr Daniel Bor wrote a thoughtful post on The dilemma of weak neuroimaging papers. He covered corrected and uncorrected statistics, a culture of sloppy neuroimaging publications, and whether a bad paper can be harmful or should be retracted.

Does Discarding Mean Retraction?

By "discarding" I meant disregarding the results from flawed articles, not retracting them from the literature entirely. This point was misunderstood by some. It seems that all commenters on Bor's post agreed that retraction is problematic.

Neuroskeptic: "Retracting them all… never going to happen, but even it did, I don’t think it would help at all. Much better would be for readers to educate themselves or be educated to the point where they know how to spot sloppy stats."

Bishop: "I don’t think it’s realistic to expect a retraction, and certainly not just on the basis of reporting of uncorrected statistics. I think we should disregard the results of this study because of the constellation of methodological problems..."

Poldrack: "I think retraction of papers that report uncorrected statistics is a bit much to ask for; after all, most of the results that were published in the days before rigid statistical corrections were common have turned out to replicate, and indeed large-scale meta-analyses have shown a good degree of consistency..."

So to get back to those Retraction Watch threads to which we referred: Yes, failure to replicate seems a good reason to retract. And notices should explain what went wrong. Allowing authors to get away with failing to do so, in some well-intentioned but misguided attempt to lower the barrier to retractions — as the Journal of Neuroscience does, for example — is part of why some people seem to think that retractions mean fraud.

This story and controversy is still evolving. To retract the paper now, without evidence of overt fraud or negligence, will mark it with the scarlet watermark of fraud. Because a retraction is the foremost boner-killer of science, the retraction is a weapon to be wielded carefully. It should be used in cases of fraud and negligence, but not in cases where there remains active debate or inconclusive evidence.

Even then, there is value to leaving errors and conflict in the literature and there must be a better tool than the retraction watermark...

Gone are the days of tearing work from the wall. These days, disapproval often takes the form of ambiguous encouragements. Put the language of critique in your hands with this series of 12 rubber stamps. Each stamp bears of fragment of abridged feedback associated with critique.

Thursday, March 08, 2012

Public voting in the 2012 Neuro Film Festival closes today, March 8, 2012. The contest includes 105 entries, available for viewing on a YouTube channel. Some videos cover well-known neurological disorders such as Parkinson's disease, epilepsy, and dementia.

Other entries feature lesser-known disorders such as Central Pain Syndrome (CPS), the worst possible pain with no relief in sight. A Message from Hell educates the public about the immense suffering experienced by patients with CPS and encourages researchers to study this neurological condition. "Doesn't every pharmaceutical company want to find a disease that isn't fatal and requires constant medication to control?"

While brushing his teeth, a 47 year old man suffered a carotid artery dissection that caused a major stroke in his right hemisphere, leaving his left side mostly paralyzed. He describes some bizarre theories and hallucinations he experienced while hospitalized. Foremost among these was a nurse with a hemicraniectomy who was thought to be the granddaughter of Eva Braun. The images accompanying this story are definitely worth the 3:39 total viewing time. He also describes the (real) procedures involved in supercooling his blood. He is currently participating in a study with an electrical stimulation device to improve his ability to walk.

Sometimes There Can Be More Than 1 (No Walk In The Park)

Dia DiCristino was well on her way to becoming a successful opera singer when she was struck by bad health. In fact the same week she was due to sing for a very prestigious opera company's mangers, she suddenly was scheduled to have life saving brain surgery. One brain surgery turned into over 25 neurological procedures and an endless stream of medical problems that forced her to retire at only 26 years of age from her opera career.

DiCristino had an arachnoid cyst that caused hydrocephalus, or an accumulation of cerebrospinal fluid (CSF) that compressed her brain. The "More Than 1" neurological problem included palinopsia, dysphasia, aphasia, spasticity, chronic headaches, startle myoclonus, seizures, sleep apnea and more. Despite all this, the very talented DiCristino wrote and performed the music featured in this video.

Temple et al (2003) published an fMRI study of 20 children with dyslexia who were scanned both before and after a computerised intervention (FastForword) designed to improve their language. The article in question was published in the Proceedings of the National Academy of Sciences, and at the time of writing has had 270 citations. I did a spot check of fifty of those citing articles to see if any had noted problems with the paper: only one of them did so.

Bishop noted at least four major problems in the paper that invalidated the conclusions, including:

The authors presented uncorrected whole brain activation data. This is not explicitly stated but can be deduced from the z-scores and p-values. Russell Poldrack, who happens to be one of the authors of this paper, has written eloquently on this subject: “…it is critical to employ accurate corrections for multiple tests, since a large number of voxels will generally be significant by chance if uncorrected statistics are used. .. The problem of multiple comparisons is well known but unfortunately many journals still allow publication of results based on uncorrected whole-brain statistics.” Conclusion 2 is based on uncorrected p-values and is not valid.

Indeed, Dr. Russ Poldrack of the University of Texas at Austin is a leader in neuroimaging methodology and a vocal critic of shoddy design and overblown interpretations. And yes, he was an author on the 2003 paper in question. Poldrack replied to Bishop in his own blog:

I'm not convinced that every prolific scientist has skeletons in his/her closet, but it was nice to see that Poldrack acknowledged this particular bag of bones:

Dorothy notes four major problems with the study:

There was no dyslexic control group; thus, we don't know whether any improvements over time were specific to the treatment, or would have occurred with a control treatment or even without any treatment.

The brain imaging data were thresholded using an uncorrected threshold.

One of the main conclusions (the "normalization" of activation following training") is not supported by the necessary interaction statistic, but rather by a visual comparison of maps.

The correlation between changes in language scores and activation was reported for only one of the many measures, and it appeared to have been driven by outliers.

Looking back at the paper, I see that Dorothy is absolutely right on each of these points. In defense of my coauthors, I would note that points 2-4 were basically standard practice in fMRI analysis 10 years ago (and still crop up fairly often today). Ironically, I raised two of of these issues in my recent paper for the special issue of Neuroimage celebrating the 20th anniversary of fMRI, in talking about the need for increased methodological rigor...

But are old school methods entirely to blame? I don't think so. It seems that some of these errors are errors in basic statistics. At any rate, I highly recommend that you read these two posts.

Many questions remain. How self-correcting is the field? What should we do with old (and not-so-old) articles that are fatally flawed? How many of these results have replicated, or failed to replicate? Should we put warning labels on the failures?

Professor Bishop also noted specific problems at PNAS, like the "contributed by" track allowing academy members to publish with little or no peer review. The "pre-arranged editor" track is another potential issue. I suggest a series of warning labels for such articles, such as the one shown below.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.